Hemal H. Patel

Caveolae are specialized plasma membrane invaginations enriched in cholesterol and sphingolipids, playing vital roles in signal transduction, lipid regulation, membrane trafficking, and mechanoprotection. Their formation and function depend on two protein families: caveolins and cavins. Caveolins are integral membrane proteins that contribute to the membrane’s curvature and serve as scaffolds for diverse signaling molecules. Cavins support caveolins at the cytoplasmic surface to stabilize caveolar architecture and regulate key processes, including insulin signaling, nitric oxide synthase activity, and lipid droplet formation. Mutations in caveolin or cavin genes can disrupt caveolae formation and function, often impairing cholesterol handling and perturbing key signaling pathways. This has been observed in a spectrum of pathologies such as muscular dystrophies, cardiomyopathies, lipodystrophies, and various cancers. Given the importance of caveolins and cavins in membrane organization, understanding how specific mutations alter caveolin and cavin function is critical for elucidating the molecular basis of various disorders and for the development of targeted therapies. This review explores how caveolin and cavin mutations affect caveolae morphology, function, and signaling, thereby impacting physiology.

Hypertension is a major risk factor for heart failure, characterized by impaired energy metabolism and mitochondrial dysfunction. The endogenous peptide catestatin (CST) has known cardiovascular protective effects, but its role in cardiac metabolism remains unclear. Here, we show that CST regulates cardiac metabolic pathways through integrated transcriptomic and network analyses, identifying cell-type-specific gene programs that are disrupted in its absence and restored with supplementation. Comparative analysis with human heart failure datasets reveals conserved alterations in glucose and fatty acid metabolism and mitochondrial function. Functional studies demonstrate that CST restores metabolic flexibility by shifting substrate utilization toward glucose oxidation. Mechanistically, CST enhances mitochondrial ATP production by interacting with ATP synthase and improving membrane potential and enzyme activity. These findings establish CST as a key regulator of cardiac energy metabolism and reveal an endocrine–mitochondrial signaling axis with therapeutic potential for hypertension-associated heart failure.

Reflecting the global expansion of research, the British Journal of Pharmacology ( BJP ) has observed a substantial increase in the number of studies focusing on natural products. However, disparities in publication requirements between studies of synthetic small molecules and natural products have led to variable acceptance rates. Building on the progress observed following the 2020 and 2024 BJP editorial on natural products, this updated editorial aims to harmonise expectations across different research domains and promote fair and unbiased assessment of natural product studies. By standardising these criteria, the BJP reaffirms its commitment to maintaining scientific rigour whilst ensuring that the guidelines are clear and practical, thereby contributing to high‐quality research reporting that advances pharmacological science.

In the 2025 novel drug mini‐review, one can take a full measure of the ingenuity that underlies current drug design and development, despite the year's smaller harvest (46 novel drugs) compared to 2024 (53) and 2023 (70). 54% of the novel drugs are first‐in‐class (FIC). The emphasis on proteins/antibodies is maintained (~25% novel drugs in 2025), an industry trend that does not seem to abate. Fewer than half of the novel medicines address major or common disorders. Among the FIC drugs, it is worth mentioning the Na _v 1.8 channel inhibitor suzetrigine, the first non‐opioid approved to palliate acute pain; the first positive allosteric modulator of transient receptor potential melastatin 8 (TRPM8), acoltremon, that increases basal tear production in dry eye disease, a globally common disorder; lerodalcibep, a ‘third generation’ adnectin inhibitor of the protease Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) to treat elevated LDL‐c; and zoliflodacin and gepotidacin, both innovatively targeting bacterial topoisomerases to treat uncomplicated urinary tract infections. Most of the approved medicines target unmet medical need areas and/or orphan indications (the latter alone accounting for 41% of the 2025 novel drugs) by applying imaginative approaches. These approaches include: the combination of two FIC drugs, the RAF/MEK clamp avutometinib paired with the FAK/Pyk2 inhibitor defactinib, to block more efficiently the RAS–RAF–MEK–ERK/FAK oncogenic pathway in low‐grade serous ovarian cancer; fitusiran, the first RNAi therapy for haemophilia, targeting for the first time the production of the natural anticoagulant anti‐thrombin in the liver; and brensocatib, which attenuates the activation of downstream neutrophil proteases by inhibiting the protease DPP1, thereby preventing lung tissue destruction in bronchiectasis. The landscape of novel drugs approved in 2025 reveals that pharmaceutical innovation continues to advance through FIC mechanisms, sophisticated therapeutic approaches, and a strong focus on unmet medical need.

Mind-body interventions offer promising avenues for improving physical and mental health, yet the comprehensive biological effects of increasingly popular mind-body retreat interventions remain poorly understood. The neural and molecular effects of a 7-day retreat intervention combining meditation, reconceptualization, and open-label placebo healing rituals are investigated in an observational study on 20 healthy human participants randomly selected from 561 retreat participants. BOLD fMRI functional connectivity during rest and meditation and whole plasma proteomics, metabolomics, exosome-specific miRNA transcriptomics, and neurite growth and real-time metabolism cellular assays are compared pre- and post-intervention. Meditation decreases functional integration in the default mode ( p = 0.00009) and salience networks ( p = 0.000003) and decreases whole-brain modularity ( p = 0.001). Compared to pre-intervention plasma, post plasma increases in vitro neurite outgrowth ( p = 0.01), enhances glycolytic metabolism ( p = 0.008), induces upregulation of BDNF ( p = 0.001), inflammatory ( p = 0.0001), anti-inflammatory ( p = 0.03), and endogenous opioid ( p = 0.03) pathways, and modulates tryptophan metabolism ( p _FDR = 0.03) and neurotransmission-associated exosome miRNA transcripts. This intensive non-pharmacological mind-body intervention produces broad short-term neural and plasma-based molecular changes associated with enhanced neuroplasticity, metabolic reprogramming, and modulation of functional cell signaling pathways, highlighting the potential of mind-body techniques to modulate neural circuits and pathways important to health and well-being.

Diabetic cardiomyopathy (DCM) is a cardiac disorder characterized by structural and functional impairments independent of coronary artery disease. Membrane microdomains, including lipid rafts and caveolae, play a crucial role in cardiac signaling, insulin receptor trafficking, and ion channel regulation. In diabetes, disrupting these microdomains leads to impaired insulin signaling, oxidative stress, and mitochondrial dysfunction, exacerbating cardiac pathology. This review explores the role of caveolins and lipid rafts in DCM and how their dysfunction contributes to disease progression. We highlight how therapeutics used to manage diabetic patients may impact microdomain integrity. Future research should focus on targeting membrane microdomains for novel treatments.